IN VIVO TAU PET IMAGING IN EARLY-ONSET ALZHEIMER’S DISEASE AND LATE-ONSET ALZHEIMER’S DISEASE

Abstract

The objectives of this study were to compare overall tau topography, inter-regional connectivity of tau deposition between early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) and to investigate the pattern of tau spreading according to disease severity in EOAD and LOAD, with recently developed tau PET tracer, 18F-THK5351. We included total number of 197 participants including 65 patients with EOAD (onset age < 65), 54 patients with LOAD (onset age ≥ 65), 37 young participants (age < 65) and 41 elderly participants (age ≥ 65) with normal cognition. Standardized uptake value ratio (SUVR) images were calculated from 50–70 minutes 18F-THK5351 PET scans. Voxel-wise analyses and regional analyses were performed. To investigate the distinct features of inter-regional correlation of THK retention, connectivity matrices were calculated. Global retention ratios of THK were not significantly different between EOAD and LOAD. Compared to LOAD, EOAD had greater THK retention in the bilateral inferior parietal, dorsolateral prefrontal cortices, and precuneus. Meanwhile, LOAD had more THK retention in the bilateral inferior temporal, anterior cingulate cortices and basal forebrain, compared to EOAD. Connectivity matrix of inter-regional THK retention revealed loss of the cortico-limbic correlation in the EOAD. When THK retention was compared as a function of CDR stage, EOAD showed high THK retention in the association cortices at the early stages of disease (CDR 0.5) and the extent of THK retention increased with CDR. On the contrary, LOAD at CDR 0.5, showed THK retention was limited in the inferior temporal and small areas of inferior parietal cortex compared to age-matched normal control (FWE corrected, p <0.05). LOAD had greater THK retention in the brain regions where neurofibrillary tangles (NFT) deposit earlier stages of Braak & Braak staging or the regions involving cholinergic pathways. While, EOAD showed disproportionately higher THK retention in the association cortices from the early stages. These suggested NFT deposits in the patients with EOAD might not follow the known sequence of Braak & Braak staging, and may be compatible with the clinical aspects in which atypical symptoms such as parietal dysfunction are more common in EOAD, whereas memory decline are predominant in LOAD.